Sepsis is regarded as a severe systemic inflammatory response syndrome (SIRS) caused by bacterial infection such as wounds, puerperium, and diseases. The character of the SIRS is hypercytokinemia, and the blood pressure is decreased by dilation of the blood vessels caused by inflammatory materials, i.e., cytokines, and toxins secreted by infected bacteria. A significant progress of hypotension causes a lack of blood flow in each site of the body to increase a risk of causing dysfunction of each organ. In order to avoid multiple organ failure, the heart increases the heart rate to increase the blood flow. This overload on the heart causes cardiac hypofunction, which leads to a chronic lack of blood supply to important organs to cause a septic shock state, resulting in “multiple organ failure.” In spite of the establishment of treatment with antibiotics, it has been reported that the number of sepsis patients in the U.S. per year is 750,000 or more and that 210,000 of the patients die. The number of patients in Japan per year is estimated at 100,000. Against such background, development of effective prophylactic and therapeutic methods for sepsis has been highly demanded.
The main reasons of the high rate of deaths from sepsis are that the sepsis therapeutic drugs that have been developed until now are all for mere symptomatic therapy for secondary lesions caused by hypercytokinemia and there are no sepsis therapeutic drugs for hypercytokinemia itself. Management of bacteria in infectious diseases has been becoming possible by progress of antibiotics. However, even if the bacteria are killed, the cytokine-inducing activity is maintained and is even higher than that of live bacteria in some cases. Blood purifying therapy utilizing hemodialysis therapy (adsorption of cytokines in blood) has been devised as a therapeutic method for hypercytokinemia, but its effect is not constant, and invasiveness to the body is also high. Many therapeutic methods, including the methods described above, have so far been tried for hypercytokinemia in sepsis, but no drug or therapeutic method was scientifically effective in many patients. The rate of deaths from sepsis tends to decrease in recent years by the start of treatment in general ward, attempt of reducing the risk of nosocomial infection by a reduction in use of pulmonary artery catheter, and administration of antibiotics in early stages. The degree of the decrease is, however, obviously small. In also treatment of sepsis, some significant treatment, not yet being discovered, other than treatment with antibiotics may be present.
Meanwhile, as one of methods for treating acne vulgaris, which is caused by bacterial infection as in sepsis, photodynamic therapy (PDT) has conventionally been known. PDT is a therapeutic method involving both photosensitizer administration and light irradiation. 5-ALA itself is not photosensitizing, but is metabolized into a photosensitizing material, protoporphyrin IX (PPIX), in vivo. Accordingly, 5-ALA is used in cancer PDT (see for example, Patent Documents 1 to 3). Clinical examples of PDT of acne vulgaris with 5-ALA have been already reported, and the therapy shows outstanding effects (see for example, Non-patent Document 1). PDT is certainly effective against bacterial infection on the skin. However, in order to kill bacteria in blood as in a case of sepsis, the blood must be directly irradiated with light. However, the absorption wavelength suitable for exciting PPIX overlaps with the absorption spectrum of hemoglobin, and an excitation light source is required to be inserted into a blood vessel via, for example, a catheter. Thus, PDT against pathogens causing sepsis has a risk of promoting further infection and exacerbating infectious disease and is therefore impractical, though it is discussed. As a result, the investigation of the PDT against pathogens causing sepsis has not progressed. In addition, PDT can be a sterilization technology, but cannot work on the above-described hypercytokinemia.
5-ALA is known as an intermediate in a tetrapyrrole biosynthetic pathway that is widely present in animals, plants, and fungi and is usually biosynthesized from succinyl CoA and glycine by 5-aminolevulinic acid synthase. Photodynamic therapy using 5-ALA (hereinafter also referred to as “ALA-PDT”) has also been developed and is paid attention as a therapeutic method with low invasiveness and maintaining QOL. For example, a tumor diagnostic or therapeutic agent including 5-ALA has been reported. 5-ALA is also known to be useful as a prophylactic/ameliorating agent or a therapeutic agent for adult diseases, cancer, and male infertility (see for example, Patent Documents 4 to 6).